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PubMed · 10440122

Brain substrate utilisation during acute hypoglycaemia.

Abstract

AIMS/HYPOTHESIS: Our study was undertaken to examine directly the utilisation of glucose and alternative substrates, in particular amino acids, during hypoglycaemia. METHODS: Catheters were positioned in the jugular venous bulb and an artery in six healthy subjects in the overnight fasted state. Arterio-venous differences for glucose, amino acids, lactate and pyruvate were measured in the basal state, during hyperinsulinaemic euglycaemia and during hyperinsulinaemic hypoglycaemia. The subjects were studied on two different occasions, once during intravenous infusion of amino acids and once during infusion of saline. RESULTS: In the basal state the fractional extraction of glucose across the brain was 10 +/- 2%, glucose uptake accounted for 106 +/- 5% of the brain's oxidative metabolism. There was a small release of lactate and pyruvate. During hyperinsulinaemia glucose uptake continued to account for the entire fuel requirement of the brain. Hyperaminoacidaemia did not result in net amino acid uptake by the brain. During hypoglycaemia (2.4 +/- 0.2 mmol/l) fractional extraction of glucose by the brain increased (p < 0.01) and glucose uptake accounted for 90 +/- 15% of the brain's oxidative metabolism. Uptake of amino acids, lactate or pyruvate could not be detected. CONCLUSION/INTERPRETATION: 1) Brain fractional extraction of glucose increases during hypoglycaemia, 2) hyperinsulinaemia does not change fractional extraction of glucose by the brain, 3) augmented availability of amino acids does not result in brain amino acid uptake during euglycaemia or hypoglycaemia and 4) under the present study conditions glucose remains the major substrate for cerebral metabolism during hypoglycaemia; lactate or pyruvate uptake by the brain can not be detected.

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BibTeXRIS

Wahren J, K Ekberg, E Fernqvist-Forbes, S Nair. 1999. Brain substrate utilisation during acute hypoglycaemia.. https://doi.org/10.1007/s001250051231

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Early IFN-gamma production is related to the presence of interleukin (IL)-18 and the absence of IL-13 in experimental Trypanosoma cruzi infections.

Gamma-interferon (IFN-gamma) production, the hallmark of the Th1 immune response, has been shown to play a central role in the resistance to Trypanosoma cruzi infections, in particular when produced in the very early acute infection. BALB/c mice infected with T. cruzi, Tulahuén strain, reach high parasitemias during the acute phase, and their spleen cells release IFN-gamma in the second week of the infection, while those of the resistant C3H strain produce the cytokine earlier, at 2 days post-infection (pi). We studied in the spleen cells supernatants of infected BALB/c and C3H mice, the spontaneous production of cytokines involved in the induction, interleukin (IL)-18 and IL-12 p70, as well as in the downregulation, IL-13 and IL-10, of the Th1 immune response. We found that, at 2 days pi, only C3H mice produced IL-18, while IL-12 p70 was detected in both mouse strains. Moreover, at this time pi splenocytes from BALB/c mice spontaneously produced high amounts of IL-13. At 14 days pi, despite the increased levels of IL-13 and IL-10 detected in C3H mice, they still showed high concentrations of IL-18 and IL-12 p70. In contrast, spleen cells from BALB/c mice did not secrete IL-18, IL-12 p70 and IL-13 at this time pi, but produced higher amounts of IL-10 than C3H mice. Non of these cytokines was found increased in the cell supernatants of chronically infected mice. The addition of lipopolysaccharide (LPS) or Concanavalin A (Con A) to the cell cultures did not enhance the production of IL-18 and IL-12 at the time points tested. On the other hand, at 21 days pi, when parasitemia peaked, an inhibition of both the LPS induced IL-10 release and the IL-13 production upon Con A stimulation was observed in C3H, but not in BALB/c mice. We did not find an increase of IL-18, IL-10, or IL-12 p70 in the serum of the infected mice, despite the high seric IL-12 p40 concentrations reached during the infection. The data show that the different kinetics of the production of these cytokines in the spleen of both mouse strains could have a key role in the in vivo regulation of IFN-gamma production. In these experimental models, early IFN-gamma release and thus resistance to T. cruzi infection, could be related to the combined effect of both IL-18 and IL-12p70 in the absence of IL-13.

Acute Disease↗